Novel inhibitors of mTORC1 and mTORC2

Curr Opin Investig Drugs. 2010 Jun;11(6):638-45.


The PI3K/Akt/mTOR pathway is frequently activated in human cancers, and mTOR is a clinically validated target for therapeutic intervention in this pathway. The discovery of the involvement of rapamycin-insensitive mTOR complex 2 (mTORC2) in the activation of Akt, combined with the limited clinical antitumor activity of mTOR complex 1 (mTORC1)-directed rapamycin analogs, have led to the discovery of ATP-competitive selective inhibitors of the mTOR kinase that inhibit the function of both mTORC1 and mTORC2. This review describes progress in the identification of selective and novel inhibitors of mTORC1/2, focusing on the profile of inhibitors that are in clinical development.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Mechanistic Target of Rapamycin Complex 1
  • Molecular Targeted Therapy*
  • Multiprotein Complexes
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Proteins / antagonists & inhibitors*
  • Proteins / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • TOR Serine-Threonine Kinases
  • Transcription Factors / antagonists & inhibitors*
  • Transcription Factors / metabolism


  • CRTC2 protein, human
  • Multiprotein Complexes
  • Proteins
  • Transcription Factors
  • Mechanistic Target of Rapamycin Complex 1
  • TOR Serine-Threonine Kinases